The objective of this study is to explore the safety of gamma-irradiated allogeneic TALL-104 cells when placed intracranially into pediatric malignant brain tumor patients. One of the Co-PIs of this application, Dr. Santoli at the Wistar Institute, has developed a powerful cell therapy approach to cancer, which utilizes the human Interleukin-2 (IL-2)-dependent leukemic T cell line TALL-104. TALL-104 cells have markers typical of cytotoxic T cells and display MHC nonrestricted tumoricidal activity. Multiple transfers of gamma-irradiated (non-proliferating) TALL-104 cells in the absence of IL-2 into immunodeficient (SCID) mice implanted with different types of human malignancies have resulted in potent anti-tumor effects against established metastases. The same approach in leukemia-bearing immunocompetent mice has induced regression of advanced disease and protection from further relapses. Direct tumoricidal effects and induction of endogenous anti-tumor immunity is demonstrable. Multiple systemic infusions of high-dose TALL-104 cells into dogs with spontaneous refractory tumors indicate the remarkable anti-tumor efficacy and safety of this novel cell therapy approach in a model more analogous to human. Dr. Santoli has initiated Phase I trials in adults with advanced metastatic breast cancer and in children with solid refractory tumors, where TALL-104 cells are given systemically multiple times. AT UCHSC, Dr. Kruse designed an FDA approved clinical study where alloreactive cytotoxic T lymphocytes are intratumorally placed multiple times into resected brain tumor beds. Two of five patients in whom we have long-term follow-up are alive without evidence of tumor recurrence at 61 and 61 months from the start of the immunotherapy. Although promising, this clinical protocol entails labor intensive methods requiring specialized equipment for generation of the biologic. Additionally, since different donors are used at each of five treatment cycles, the biologic is different at each use. Similar to the alloreactive CTL protocol, the well-defined allogeneic TALL-104 cell line will be implanted multiple times intracranially into children wth refractory brain tumors. The study will be performed as a Phase I trial to determine the effects of dose escalation. Dr. Santoli and colleagues at the Wistar Institute will be responsible for the manufacture of clinical-grade TALL-104 cells. The team at UCHSC/TCH will conduct the trial with brain tumor patients. Dr. Kruse's laboratory will prepare the cells for infusion and perform quality control tests mandated by the FDA. Dr. Ken R. Winston, a pediatric neurosurgeon and Co-PI/Clinical Director of the study, will be responsible for the conduct of the clinical trial and patient care. Dr. Winston will administer the first set of TALL-104 cells at either 1) a debulking surgery and place a reservior/catheter system directed into the resected tumor bed for future administrations, or 2) through an existing reservoir into leptomeningeal space, or 3) by cisternal or lumbar puncture if significant spinal disease exists. Drs. Winston or Nicholas Foreman, co-investigator and pediatric oncologist, will give subsequent infusions of TALL-104 cells on the GCRC at The Children's Hospital. Drs. Kruse and Santoli will complete correlative laboratory experiments to learn about the interaction of the TALL-104 cells with the host.